In Silico Identification of miRNAs Regulating Vitamin D Receptor and Its Genetic Network in Bone Metabolism

Abstract

The vitamin D receptor (VDR), a central nuclear receptor helps to maintain bone mineral density. When its function is disturbed, it can contribute to osteoporosis development and other bone diseases. This study carried out a thorough computational analysis to identify human microRNAs (miRNAs) regulatingVDR and other genes that functionally interact with VDR. First of all, a ranked interaction network of VDR with 20 other genes has been predicted using GeneMANIA software. With the help of miRDB software, 154 candidate miRNAs are traced to target VDR by binding the VDR 3′UTR. Cross-checking with TargetScanHuman and miRTargetLink 2.0 refined these results. 11 miRNAs were supported by all three tools and another 129 were consistent between miRDB and TargetScan. Among these 11 miRNAs, miR-125b-5p and miR-2861 are reported to be promising regulators of bone remodeling and potential biomarkers of osteopororsis. Many of the identified miRNAs also target VDR interaction partners including RXRs, RUNX2, SMAD family members, MED1, TOB2, BAZ1B, and NCOA1 suggesting coordinated regulation of the VDR signalling module. Available literatures supported that several of these miRNAs are dysregulated in bone-related conditions such as osteoporosis, osteosarcoma, osteoarthritis, and rheumatoid arthritis, underscoring their likely biological relevance. This integrated list is presented here as a prioritized resource of VDR-associated miRNAs and their potential network targets. Several well-supported and novel candidates such as miR-125b-5p and miR-2861 emerge as promising targets for experimental validation as biomarkers or therapeutic modulators of skeletal diseases. Overall, the results highlight the layered, post-transcriptional control of VDR and provide a roadmap for focused functional studies.